A close one-on-one transmembrane interaction between cytoplasmic actin microfilaments and extracellular fibronectin-containing fibers was recently observed by us using transmission electron microscopy, goniometry, and immunological labeling methods on hamster and human fibroblasts in vitro. We call this actin-fibronectin association the fibronexus. Others have found that neoplastically transformed cells are defective in binding surface fibronectin, and some workers have considered this property to be the in vitro hallmark of highly metastatic tumor cells. We propose that such invasive cells have alterations in their fibronexuses which are at least partially responsible for their atypical surface affinities towards fibronectin, and that such changes may contribute to their aberrant social properties. Experiments utilizing immunoelectron microscopy, freeze-etching, biochemical affinity methods will be performed to define precisely the properties of fibronexuses in normal cells, and the possible changes which occur following transformation. An important aspect of these studies will focus on the isolation and characterization of intramembranous ligands between fibronectin and actin in normal and transformed cells. Finally, the relevance of these observations to the metastatic and invasive properties of human tumors will be established by direct studies on epidermal and colon carcinomas obtained from cancer patients.